CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP
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ORIGINAL ARTICLE
CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP C. C. Liu,1 H. L. Zhang,1 L. L. Zhi,2 P. Jin,1 L. Zhao,1 T. Li,1 X. M. Zhou,1 D. S. Sun,3 G. H. Cheng,4 Q. Xin,4 L. Shi,1,5 and M. Xia1,5
The maturation of dendritic cells is critical for chronic rhinosinusitis with nasal polyps (CRSwNPs), especially eosinophilic chronic rhinosinusitis with nasal polyps (EosCRSwNPs), but the regulation mechanism of dendritic cells (DCs) maturation is still unclear. We identified nasal mucosa of 20 patients with EosCRSwNP, 16 non-EosCRSwNP patients, and inferior turbinate of 14 patients with nasal septum deviation after surgery. The expression of cyclin-dependent kinase 5 (CDK5) and programmed cell death 1 ligand 1 (PDL1) were detected by immunofluorescent, real-time quantitative PCR, and Western blot in EosCRSwNP. The level of dendritic cell maturation was detected by flow cytometry and immunofluorescence staining after CDK5 expression interference with small interfering RNA (siRNA). The expression of CDK5 and PD-L1 in EosCRSwNP nasal mucosal tissue was significantly higher than that of non-EosCRSwNP and inferior turbinate nasal mucosa tissue, and there was a positive correlation between them. Immunofluorescence staining showed that CDK5 and PD-L1 were co-localized in dendritic cells. Synergistic stimulation of dendritic cells with LPS and TNF-α promotes the maturation of dendritic cells and increases the expression of CDK5 and PD-L1. However, blocking the expression of CDK5 in dendritic cells with siRNAs leads to a blockage of cell maturation. CDK5 can regulate the expression of PD-L1, and its presence is critical for the maturation of dendritic cells. CDK5 may play an important role in the pathogenesis of CRSwNP disease.
Abstract—
KEY WORDS: CDK5; PD-L1; CRSwNP; dendritic cells; maturation; inflammatory. C. C. Liu, H. L. Zhang, L. Shi and M. Xia contributed equally to this work.
INTRODUCTION
1
Department of Otolaryngology, The Second Hospital of Shandong University, Shandong University, No.274 Beiyuan Road, Jinan, 250033, Shandong Province, China 2 Department of Otolaryngology, The Central Hospital of Zibo, No.54, Gongqingtuan West Road, Zhangdian District, Zibo, Shandong Province, China 3 Central Laboratory, The Second Hospital of Shandong University, Shandong University, No.274 Beiyuan Road, Jinan, Shandong Province, China 4 Department of Cancer Center, The Second Hospital of Shandong University, Shandong University, No.274 Beiyuan Road, Jinan, Shandong Province, China 5 To whom correspondence should be addressed at Department of Otolaryngology, The Second Hospital of Shandong University, Shandong University, No.274 Beiyuan Road, Jinan, 250033, Shandong Province, China. E-mails: [email protected]; [email protected]
Chronic rhinosinusitis (CRS) is a chronic inflammatory disease that mainly occurs in the nasal-sinus mucosa, and has a high incidence rate and severely affects the quality of life of patients [1–3]. CRS is classified into CRS without nasal polyps (CRSsNP) and w
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